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幽门螺杆菌调节 S-1 辅助化疗胃癌患者的宿主免疫。

Helicobacter pylori Modulated Host Immunity in Gastric Cancer Patients With S-1 Adjuvant Chemotherapy.

机构信息

Division of Biomedical Research and Development, Iwate Medical University Institute for Biomedical Sciences, Yahaba, Japan.

Aspiring Scientists Summer Internship Program, George Mason University, Manassas, VA, USA.

出版信息

J Natl Cancer Inst. 2022 Aug 8;114(8):1149-1158. doi: 10.1093/jnci/djac085.

Abstract

BACKGROUND

Paradoxically, Helicobacter pylori-positive (HP+) advanced gastric cancer patients have a better prognosis than those who are HP-negative (HP-). Immunologic and statistical analyses can be used to verify whether systemic mechanisms modulated by HP are involved in this more favorable outcome.

METHODS

A total of 658 advanced gastric cancer patients who underwent gastrectomy were enrolled. HP infection, mismatch repair, programmed death-ligand 1 (PD-L1) and CD4/CD8 proteins, and microsatellite instability were analyzed. Overall survival (OS) and relapse-free survival (RFS) rates were analyzed after stratifying clinicopathological factors. Cox proportional hazards regression analysis was performed to identify independent prognostic factors.

RESULTS

Among 491 patients that were analyzed, 175 (36%) and 316 (64%) patients were HP+ and HP-, respectively. Analysis of RFS indicated an interaction of HP status among the subgroups for S-1 dose (Pinteraction = .049) and PD-L1 (P = .02). HP+ patients in the PD-L1- group had statistically higher 5-year OS and RFS than HP- patients (81% vs 68%; P = .0011; hazard ratio [HR] = 0.48, 95% confidence interval [CI] = 0.303 to 0.751, and 76% vs 63%; P = .001; HR = 0.508, 95% CI = 0.335 to 0.771, respectively). The 5-year OS and RFS was also statistically higher for HP+ compared with HP- patients in the "PD-L1- and S-1-r educed" group (86% vs 46%; P = .001; HR = 0.205, 95% CI = 0.07 to 0.602, and 83% vs 34%; P = .001; HR = 0.190, 95% CI = 0.072 to 0.498, respectively). Thus, HP status was identified as one of the most potentially important independent factors to predict prolonged survival.

CONCLUSION

This retrospective study suggests that an HP-modulated host immune system may contribute to prolonged survival in the absence of immune escape mechanisms of gastric cancer.

摘要

背景

具有讽刺意味的是,幽门螺杆菌阳性(HP+)的晚期胃癌患者的预后优于 HP 阴性(HP-)的患者。免疫和统计分析可用于验证 HP 调节的全身机制是否参与了这种更有利的结果。

方法

共纳入 658 例接受胃切除术的晚期胃癌患者。分析 HP 感染、错配修复、程序性死亡配体 1(PD-L1)和 CD4/CD8 蛋白以及微卫星不稳定性。对临床病理因素进行分层后,分析总生存期(OS)和无复发生存期(RFS)。采用 Cox 比例风险回归分析确定独立预后因素。

结果

在 491 例可分析的患者中,175 例(36%)和 316 例(64%)患者为 HP+和 HP-,分别。RFS 分析表明,HP 状态与 S-1 剂量亚组之间存在交互作用(Pinteraction =.049)和 PD-L1(P =.02)。PD-L1-组中 HP+患者的 5 年 OS 和 RFS 显著高于 HP-患者(81% vs 68%;P =.0011;HR = 0.48,95%CI = 0.303 至 0.751,和 76% vs 63%;P =.001;HR = 0.508,95%CI = 0.335 至 0.771)。与 HP-患者相比,在“PD-L1-和 S-1 减少”组中,HP+患者的 5 年 OS 和 RFS 也更高(86% vs 46%;P =.001;HR = 0.205,95%CI = 0.07 至 0.602,和 83% vs 34%;P =.001;HR = 0.190,95%CI = 0.072 至 0.498)。因此,HP 状态被确定为预测生存期延长的最重要的独立因素之一。

结论

这项回顾性研究表明,HP 调节的宿主免疫系统可能有助于在没有胃癌免疫逃逸机制的情况下延长生存时间。

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